PROJECT SUMMARY/ABSTRACT Understanding the basic neural mechanisms underlying stuttering is widely acknowledged as fundamental to informed diagnosis and treatment. The required cornerstone for this important knowledge is a theoretical framework of stuttering that accounts for various primary and associated speech characteristics, and that is consistent with empirically-verified models of sensorimotor control and neural functioning. The research program proposed here takes a comprehensive neurobiological approach to developing a mechanistic model of stuttered speech dysfluencies through an integrated series of theoretically-motivated, hypothesis-driven, state-of-the art experiments. A common theme throughout the proposed experiments is the fact that the neural control of movement depends on dynamically adjusted bidirectional interactions between efferent and afferent systems. The direct aim is to elucidate these sensorimotor interactions and their role in stuttered speech. Based on empirical and computational work suggesting that the CNS is able to control fast voluntary movements by continually predicting future sensory states, our lab recently found in multiple studies that typical speakers modulate auditory processing mechanisms prior to the initiation of speech movements, but that this mechanism is entirely lacking in adults who stutter. Thus, predictive modulatory mechanisms prove to be a particularly powerful model for elucidating the mechanisms underlying speech motor breakdowns in stuttering. The individual experiments within this program of research are designed to determine whether stuttering individuals? well-documented deficit in pre-speech auditory modulation is already present in childhood close to stuttering onset, whether this deficit is specific to motor-to-auditory interactions or also affects processing in the somatosensory domain, and to uncover various aspects of the phenomenon?s functional relevance in speech sensorimotor control. The proposed studies comparing both children and adults who stutter with typically fluent speakers have the potential to offer mechanistic insights into the development and limitations of the speech sensorimotor system in this common disorder of speech fluency. Specifically, crucial new insights will be gained into the involvement of sensorimotor interactions in feedback monitoring mechanisms that have long been hypothesized to play a fundamental role in the physiological basis of stuttering. Moreover, these findings will offer suggestions for novel treatment approaches such as non-invasive brain stimulation of neural pathways involved in pre-movement motor-to-sensory signaling. Thus, this work's direct relevance to public health lies in its contributions to understanding the neural mechanisms underlying stuttering and ? by generating such new insights ? facilitating the development of improved approaches to diagnosis and treatment.